Electroporation, or electropermeabilization, is the phenomenon in which cell membrane permeability to ions and macromolecules is increased by exposing the cell to short (microsecond to millisecond) high voltage electric field pulses (E. Neumann, M. Schaeffer-Ridder, Y. Wang, P. H. Hofschneider, Gene transfer into mouse lymphoma cells by electroporation in high electric fields, EMBO J 1 (1982) 841-845.). Experiments show that the application of electrical pulses can have several different effects on the cell membrane, as a function of various pulse parameters; such as amplitude, length, shape, number of repeats and intervals between pulses. As a function of these parameters, the application of the electrical pulse can have no effect, can have a transient permeabilization effect known as reversible electroporation or can cause permanent permeabilization known as irreversible electroporation. Both, reversible and irreversible electroporation have important application in biotechnology and medicine.
Reversible electroporation is now commonly used with micro-organisms and cells in culture for transfection and introduction or removal of macromolecules from individual cells. Irreversible electroporation is used for sterilization of liquid media from micro-organisms. During the last decade reversible electroporation has started to be used in living tissues for in vivo gene therapy (electrogenetherapy) (M. J. Jaroszeski, R. Heller, R. Gilbert, Electrochemotherapy, electrogenetherapy, and transdermal drug delivery: electrically mediated delivery of mollecules to cells, Humana Press, Totowa, N.J., 2000; D. A. Dean, Nonviral gene transfer to skeletal, smooth, and cardiac muscle in living animals, Am J Physiol Cell Physiol 289 (2005) C233-245; L. M. Mir, P. H. Moller, F. Andre, J. Gehl, in Advances in Genetics, Academic Press, 2005, pp. 83-114) and to enhance the penetration of anti-cancer drugs into undesirable cells (electro-chemotherapy) (A. Gothelf, L. M. Mir, J. Gehl, Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation, Cancer Treat. Rev. 29 (2003) 371-387). Recently, irreversible electroporation has also found a use in tissues as a minimally invasive surgical procedure to ablate undesirable tissue without the use of adjuvant drugs (R. V. Davalos, L. M. Mir, B. Rubinsky, Tissue Ablation with Irreversible Electroporation, Ann. Biomed. Eng. 33 (2005) 223; L. Miller, J. Leor, B. Rubinsky, Cancer cells ablation with irreversible electroporation, Technology in Cancer Research and Treatment 4 (2005) 699-706; J. Edd, L. Horowitz, R. V. Davalos, L. M. Mir, B. Rubinsky, In-Vivo Results of a New Focal Tissue Ablation Technique: Irreversible Electroporation, IEEE Trans. Biomed. Eng. 53 (2006) 1409-1415).
Electroporation is a dynamic phenomenon that depends on the local transmembrane voltage at each cell membrane point. It is generally accepted that for a given pulse duration and shape, a specific transmembrane voltage threshold exists for the manifestation of the electroporation phenomenon (from 0.5V to 1V). This leads to the definition of an electric field magnitude threshold for electroporation (Eth). That is, only the cells within areas where E≧Eth are electroporated. If a second threshold (Eth_irr) is reached or surpassed, electroporation will compromise the viability of the cells, i.e., irreversible electroporation.
Precise control over the electric field that develops in tissues is important for electroporation therapies (J. Gehl, T. H. Sorensen, K. Nielsen, P. Raskmark, S. L. Nielsen, T. Skovsgaard, L. M. Mir, In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution, Biochimica et Biophysica Acta 1428 (1999) 233-240; D. Miklavcic, D. Semrov, H. Mekid, L. M. Mir, A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy, Biochimica et Biophysica Acta 1523 (2000) 73-83; D. Miklavcic, K. Berays, D. Semrov, M. Cemazar, F. Demsar, G. Sersa, The Importance of Electric Field Distribution for Effective in vivo Electroporation of Tissues, Biophys. J. 74 (1998) 2152-2158). For instance, in reversible electroporation it is desirable to generate a homogeneous electric field (Eth≦E<Eth—irr) in the region of interest and a null electric field in the regions not to be treated. Currently, optimization of the electric field distribution during electroporation is done through design of optimal electrode setups (G. A. Hofmann, in M. J. Jaroszeski, R. Heller, R. A. Gilbert (Editors), Electrochemotherapy, electrogenetherapy and transdermal drug delivery: electrically mediated delivery of molecules to cells, Humana Press, Totowa, N.J., 2000, pp. 37-61). However, there are situations in which an electrode setup alone is not sufficient for obtaining an optimal electrical field, particularly in situations such as the electroporation of irregularly shaped tissues or when the protection of specific tissue regions is required.